FDA Takes Unprecedented Measures to Promote Rapid Development of Coronavirus Diagnostic Tests

The FDA is following a two-prong strategy to promote and expedite development and validation of a test capable of safe, rapid and reliable detection of novel coronavirus (COVID-19), the disease caused by the SARS-CoV-2 virus. Here’s an overview of the progress being made—and not made—on both fronts. The Traditional EUA Pathway The FDA is calling on test makers to seek rapid approval via the emergency use authorization (EUA) pathway the way it did with SARS, H1N1 and other previous outbreaks. The problem is that novel coronavirus isn’t a known pathogen the way the previous outbreak viruses were. As a result, the diagnostics have to be created from scratch. The other issue is time. Historically, it takes months to secure EUA clearance. The good news is that the FDA has streamlined its application process by implementing a rolling process using an electronic template. The agency reports that it has already contacted more than 70 test makers interested in seeking EUA for coronavirus detection tests. In fact, the agency has already broken its own speed record by issuing its first EUA on February 4, less than a week after mobilizing the pathway, for a reverse transcriptase real-time PCR (rRT-PCR) assay (aka, the 2019 Real Time RT-PCR Diagnostic Test Panel) developed by the U.S. Centers for Disease Control and Prevention (CDC). The test was approved for use only by CDC-designated labs certified to perform high-complexity testing in accordance with agency protocol. The CDC has distributed test kits to state health departments and public health labs around the country. But reagent, instrumentation and lab staff shortages, coupled with questions about the test’s reliability in ruling out infection, has made the pace of test validation and deployment frustratingly slow. As of March 10, the CDC reports that that 78 public health labs are now running the test. Those labs have the current capacity to test 75,000 people, which is not nearly enough. To address the reagent bottlenecks, the FDA extended the CDC’s EUA to cover kit lots from reagent two manufacturers validated at CDC labs, including two kit lots from Integrated DNA Technologies (IDT), which is owned by Danaher, and one kit lot from LGC Biosearch Technologies. But the shortages continue. In addition to the CDC assay, the FDA has recently issued EUA for two commercial tests:

• On March 12, EUA was granted to the Cobas SARS-CoV-2 rRT-PCR assay from Roche for qualitative detection used with the Cobas 6800 and 8800 systems; and
• On March 13, the FDA provided EUA clearance to Thermo Fisher Scientific’s TaqPath COVID-19 Combo Kit, is for the qualitative detection of SARS-CoV-2 nucleic acid in nasopharyngeal swab, nasopharyngeal aspirate, and bronchoalveolar lavage specimens from individuals suspected of having COVID-19 by their healthcare provider.

As of March 16, Thermo Fisher had 1.5 million tests available to ship under the EUA label and expects to increase production to reach 2 million tests per week. Based on available raw materials and the installed instrument base, the firm expects to ramp up production to up to 5 million tests per week in April. Thermo Fisher plans to initially ship those tests to approximately 200 laboratories in the U.S. and “will continue to work in partnership with government agencies and private partners to expand access,” according to a company statement. In addition, to the two commercial assays, the FDA gave EUA to the Wadsworth Center, New York State Department of Public Health’s New York SARS-CoV-2 RT-PCR Diagnostic Panel authorized for emergency use by a pair of public laboratories in the state. The flow of EUA tests is expected to accelerate with Qiagen and GenMark Diagnostics among the manufacturers with assays in the pipeline. Non-EUA Pathway For the first time, emergency development of new pathogen testing in the U.S. isn’t confined to the EUA pathway. The FDA is also pursuing a second strategy of allowing high-complexity CLIA labs (of which there are a reported 300 to 400 across the country) to develop and start using validated coronavirus tests before the agency even completes review of their EUA applications. High-complexity labs are required to strictly follow CDC testing protocols, notify the FDA of test validation and submit a complete EUA request within 15 days after validation. Among the first labs to follow this unprecedented pathway is LabCorp, which launched its LabCorp 2019 Novel Coronavirus (COVID-19) NAA test on March 6. Like the EUA tests, the LabCorp assay uses PCR technology to qualitatively detect the SARS-CoV-2 virus from respiratory samples collected at the point of care. Other major labs planning to launch their own SARS-CoV-2 tests prior to completion of EUA review include Quest Diagnostics, BioReference Laboratories (part of Opko Health) and Enzo Biochem. Takeaway Creating tests capable of detecting new pathogens is always a slow process. What makes the coronavirus situation different is that the pathogen was previously unknown, meaning that test makers didn’t get the benefit of the head start they had with previous outbreak viruses. The speed of the coronavirus spread and growing urgency of the public health crisis makes the delay in test development all the more frustrating, not to mention dangerous. The good news is that it’s not business as usual. The imperative for rapid test development is unprecedented; and so are the regulatory strategies being followed to ensure the development and deployment of a reliable coronavirus detection test as soon as possible. Scorecard: Corona Testing & the European MarketWhile the pace of approval for new coronavirus diagnostic tests in the U.S. is faster than in any previous infectious illness outbreak, it’s still far behind Europe where have already reached the market. Such tests include: Coronavirus Assays Receiving CE-IVD Marking in Europe (in rough chronological order of approval date)

Test Maker	Coronavirus Detection Test
Primerdesign (owned by Novacyt)	Molecular SARS-CoV-2 virus test for research-use-only
Co-Diagnostics	Logix Smart Coronavirus COVID-19 test
Snibe Diagnostic	Maglumi 2019-nCoV (SARS-CoV-2) IgM/IgG kits
BGI	Real-Time Fluorescent RT-PCR kit for detecting SARS-CoV-2 virus
EliTech Group	GeneFinder COVID-19 RealAmp kit for SARS-CoV-2 detection
Genomica (owned by PharmaMar Group)	qCOVID-19 and CLART COVID-19 kits
CerTest BioTec	ViaSure SARS-CoV-2 Real Time PCR Detection Kit
Genematrix	Neoflex COVID-19 coronavirus test kit